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Although Northrop Frye once indicated that Gulliver’s Travels is a Menippean satire (308), an obscure genre that has lately got increasing attentions,1 the specific ways the text stands as the genr...

Once cells have been used to produce biochemicals, there are only a few effective ways to utilize the residual cell mass, even though the utilization of leftover cells would aid in decreasing production costs. Here, a polyhydroxybutyrate (PHB) and isobutanol co-production system was designed to address this challenge. The addition of the PHB operon into Escherichia coli conferred a metabolic advantage for alcohol production, generating 1.14-fold more isobutanol. Furthermore, following nitrogen source optimization and cofactor engineering, the engineered E. coli strain produced 2-fold more isobutanol and 0.25 g/L PHB. Moreover, E. coli cells showed higher tolerance to isobutanol with the overexpression of PHB biosynthesis genes. This co-production system resulted in an increased biomass, higher glucose utilization, and lower acetate maintenance, leading to higher productivity regarding PHB and isobutanol yield. Thus, this novel system is applicable to future fermentation studies for the co-production of PHB and isobutanol.

This paper presents the first CMOS Vascular Endothelial Growth Factor (VEGF) sensor for cancer diagnosis directly from human blood. The sensor incorporates a peptide aptamer-based microneedle that allows the detection of electrochemical reactions with VEGF. This results in a capacitance change between the microneedles and then reads out by a two-step capacitance-to-digital converter (CDC). The proposed two-step CDC consists of a coarse 5b slope ADC and a fine 14b continuous-time delta-sigma modulator (CTDSM). During slow peptide-binding, the slope ADC performs a coarse conversion and the results are used to adjust the current level of the stimulator. After settling of the peptide-binding, based on an adjusted stimulation current, the CTDSM measures the small capacitance changes of the sensor. The prototype chip is fabricated in a 65-nm CMOS process, occupying a 0.87 mm $^{2}$ active area. The power consumption is 270 muW. Thanks to the two-step approach, this work achieves a wide dynamic range of 18.3b, covering a large sensor-to-sensor variation. It also achieves a peak resolution of 13.7b, while maintaining $ errors in 1 to 100 nF baseline capacitance. The overall sensor system successfully detects the VEGF in both phosphate-buffered saline (PBS) and human blood serum. Without the use of precision instruments, this work achieves a resolution of 15 fM $_{\text{rms}}$ in range of 0.1 to 1000 pM and denotes the clear VEGF selectivity at 40× in PBS and 5× in the blood serum compared to other proteins (IgG, Con A, and cholera toxin).

A malignant tumor consists of rapidly growing cancer cells, and requires a dedicated blood supply to provide oxygen and nutrients. Therefore, vascular endothelial growth factor (VEGF), a signal protein produced by cells stimulating angiogenesis, is considered as a key biomarker in clinical diagnosis of cancers [1], [2]. There are already existing methods for the VEGF detection requiring advanced instruments and complex protocols [2]. Recently, significant progress has been achieved in biosensors for the detection and quantification of VEGF using synthetic receptors [2]. In particular, a capacitive biosensor detects the change of dielectric properties when the receptor binds to VEGF, and capacitance change can be used to quantify the reactions. However, the sensitivity of the capacitive biosensors still needs to be improved for use in cancer diagnosis.

To assess the clinical characteristics of the rare Kluyvera ascorbata infection, we reviewed the medical records of patients from whom K. ascorbata was isolated from 2010 to 2016, and conducted a systematic review of the English and Spanish literature in PubMed for reports of K. ascorbata infection in humans from 1971 to 2018. A total of 43 cases (24 adults and 19 children) were enrolled: 3 at our hospital and 40 from the literature review. The urinary tract was the most common site of infection (44.2%, 19/43), followed by the bloodstream (27.9%, 12/43). There was no significant difference in the frequency of urinary tract infections (50% vs 36.8%; P = 0.388) and bloodstream infections (25% vs 31.6%; P = 0.633) in adults and children. Seventeen (60.7%, present in 28 of 43 cases) had nosocomial or healthcare-associated infections: 72.7% among children and 60% among adults. Superinfection developed in 20% (6 in 30 cases). The overall mortality was 12.1%. The antimicrobial agents mainly used in these 43 cases were third-generation cephalosporin, cefepime, piperacillin-tazobactam, ciprofloxacin, amikacin, and carbapenem. Most strains were resistant to ampicillin and first- and second-generation cephalosporins. K. ascorbata is a rare but significant clinical pathogen in adults and children.

Nontuberculous mycobacteria are ubiquitous environmental organisms that are rare pathogens in immunocompetent individuals. However, cutaneous nontuberculous mycobacteria infections have been increasingly associated with invasive procedures, including surgery, liposuction, filler injection, intramuscular injection, mesotherapy, piercing, acupuncture, and cupping therapy. Herein, we report the first case of cutaneous nontuberculous mycobacteria infection caused by the East-Asian traditional treatment ‘Gua Sha’, also known as scraping, coining or spooning in English. A 35-year-old healthy female presented with widespread, painful skin nodules and pustules on her upper and lower extremities that had developed after Gua Sha treatment for body contouring. Histopathologic examination of the lesions revealed granulomatous inflammation in the dermis and the culture isolates were identified as Mycobacterium massiliense with molecular identification. The patient was successfully treated with intermittent incision and drainage of persistent nodules and oral clarithromycin based on antimicrobial susceptibility testing. We recommend implementation of a standard safety protocol for Gua Sha practitioners to minimize the risk of infection transmission.

// Il Minn 1 , Soo Min Koo 1 , Hye Soo Lee 1 , Mary Brummet 1 , Steven P. Rowe 1 , Michael A. Gorin 2 , Polina Sysa-Shah 1 , William D. Lewis 1 , Hye-Hyun Ahn 1 , Yuchuan Wang 1 , Sangeeta Ray Banerjee 1 , Ronnie C. Mease 1 , Sridhar Nimmagadda 1 , Mohamad E. Allaf 2 , Martin G. Pomper 1 , Xing Yang 1 1 Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA 2 The James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA Correspondence to: Martin G. Pomper, email: mpomper@jhmi.edu Xing Yang, email: xyang45@jhmi.edu Keywords: carbonic anhydrase IX, positron emission tomography, molecular imaging, renal cell carcinoma, copper-64 Received: February 25, 2016 Accepted: June 09, 2016 Published: July 14, 2016 ABSTRACT Carbonic anhydrase IX (CAIX) is a cell surface enzyme that is over-expressed in approximately 95% of cases of clear cell renal cell carcinoma (ccRCC), the most common renal cancer. We synthesized and performed in vitro and in vivo evaluation of a dual-motif ligand, [ 64 Cu]XYIMSR-06, for imaging CAIX expression on ccRCC tumors using positron emission tomography (PET). [ 64 Cu]XYIMSR-06 was generated in yields of 51.0 ± 4.5% (n=5) and specific activities of 4.1 – 8.9 GBq/μmol (110-240 Ci/mmol). Tumor was visualized on PET images by 1 h post-injection with high tumor-to-background levels (>100 tumor-to-blood and -muscle) achieved within 24 h. Biodistribution studies demonstrated a maximum tumor uptake of 19.3% injected dose per gram of radioactivity at 4 h. Tumor-to-blood, -muscle and -kidney ratios were 129.6 ± 18.8, 84.3 ± 21.0 and 2.1 ± 0.3, respectively, at 8 h post-injection. At 24 h a tumor-to-kidney ratio of 7.1 ± 2.5 was achieved. These results indicate pharmacokinetics superior to those of previously reported imaging agents binding to CAIX. [ 64 Cu]XYIMSR-06 is a new low-molecular-weight PET ligand targeting CAIX, which can image localized and metastatic ccRCC.

A Gram-stain-positive, catalase-positive, facultatively anaerobic, non-motile, coryneform bacterium, designated strain 32T, was isolated from a closed pus sample from a patient having finger necrosis in Korea. Strain 32T was considered as representing a novel species according to its initial identification by matrix-assisted laser desorption/ionization-time-of-flight MS. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain 32T belonged to the genus Dermabacter and was closely related to Dermabacter hominis DSM 7083T (=ATCC 49369T) (98.34 % similarity). Optimal growth was observed at 30-40 °C and pH 7. Growth occurred in the presence of 0-6 % (w/v) NaCl. Menaquinones MK-8, MK-7 and MK-9 were the major respiratory quinones. The major polar lipids were phosphatidylethanolamine, phosphatidylcholine, glycolipid and two unknown lipids. The major cellular fatty acids were anteiso-C17 : 0, anteiso-C15 : 0, iso-C16 : 0 and iso-C15 : 0. The DNA G+C content of strain 32T was 62.58 mol%, and the mean level of DNA-DNA relatedness between strain 32T and D. hominis ATCC 49369T was 49±1.6 %. Based on the phenotypic and genotypic characteristics, strain 32T is confirmed to represent a novel species of the genus Dermabacter, for which the name Dermabacter jinjuensis sp. nov. is proposed. The type strain is 32T (=NCCP 16133T=DSM 101003T).

Variant Philadelphia chromosome translocations involving chromosomes other than 9 and 22 have been reported in 5-10% of patients with chronic myeloid leukemia (CML). As part of the three-way variant t(9;22;11) in patients with CML, 11q24 is a novel region that has not previously been investigated. A 22-year-old male exhibiting chronic phase CML developed a recurrence of the same phase subsequent to the interruption of imatinib treatment and showed the same chromosomal abnormality, t(9;22;11)(q34;q11.2;q24), that was detected at the initial diagnosis. The recurrent CML responded well to imatinib therapy. These findings suggest that the three-way variant, t(9;22;11), involving 11q24 may be associated with a good prognosis and response to imatinib. This is the first report of three-way variant involving 11q24 in a patient with CML.

The overuse of antibiotics has led to the emergence of multidrug-resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA). MRSA is difficult to kill with a single antibiotic because it has evolved to be resistant to various antibiotics by increasing the PBP2a (mecA) expression level, building up biofilm, introducing SCCmec for multidrug resistance, and changing its membrane properties. Therefore, to overcome antibiotic resistance and decrease possible genetic mutations that can lead to the acquisition of higher antibiotic resistance, drug combination therapy was applied based on previous results indicating that MRSA shows increased susceptibility to free fatty acids and surfactants. The optimal ratio of three components and the synergistic effects of possible combinations were investigated. The combinations were directly applied to clinically isolated strains, and the combination containing 15 &mu, g/mL of oxacillin was able to control SCCmec type III and IV isolates having an oxacillin minimum inhibitory concentration (MIC) up to 1024 &mu, g/mL, moreover, the combination with a slightly increased oxacillin concentration was able to kill SCCmec type II. Phospholipid analysis revealed that clinical strains with higher resistance contained a high portion of 12-methyltetradecanoic acid (anteiso-C15:0) and 14-methylhexadecanoic acid (anteiso-C17:0), although individual strains showed different patterns. In summary, we showed that combinatorial therapy with a low concentration of oxacillin controlled different laboratory and highly diversified clinical MRSA strains.

Aim Colon cancer is one of the leading causes of cancer-related mortality. However, specific biomarkers for its diagnosis or treatment are not established well. Methods We developed a colon-cancer specific peptide probe using phage display libraries. We validated the specificity of this probe to colon cancer cells with immunohistochemical staining and FACS analysis using one normal cell and five colon cancer cell lines. Results This peptide probe maintained binding affinity even after serum incubation. For therapeutic applications, this peptide probe was conjugated to hematoporphyrin, a photosensitizer, which showed a significantly enhanced cellular uptake and high photodynamic effect to kill tumor cells. As another application, we made a nanoparticle modified from the peptide probe. It efficiently delivered SN-38, an anticancer drug, into tumor cells, and its tumor-targeting ability was observed in vivo after intravenous injection to the same xenograft model. Conclusion The noble dodecapeptide probe can be a promising candidate for both colon tumor diagnosis and targeted drug delivery.

Candida glabrata bloodstream infection (BSI) isolates from a particular geographic area have been reported to comprise a relatively small number of the major sequence types (STs) by multilocus sequence typing (MLST) analysis. Yet little is known about the characteristics of major ST strains of C. glabrata. To address this question in Korea, we investigated antifungal resistance and non-synonymous mutations of the mismatch repair gene (msh2 mutations) in C. glabrata BSI isolates, as well as associated clinical characteristics, and compared the results according to MLST genotype. We assessed a total of 209 C. glabrata BSI isolates from seven hospitals in Korea for 2 years (2009 and 2014). Clinical features of candidemia and their outcomes were analyzed for 185 available cases. According to MLST, ST7 (47.8%) was the most common type, followed by ST3 (22.5%); the remainder represented 28 types of minor STs (29.7%). Fluconazole-resistance (FR) rates for ST7, ST3, and other strains were 9.0% (9/100), 8.5% (4/47), and 4.8% (3/62), respectively, and all were susceptible to amphotericin B and micafungin. All ST7 isolates harbored the V239L mutation in msh2, known to confer hypermutability, while 91.5% of ST3 isolates did not harbor the msh2 mutation. Overall, isolates of the same ST had identical msh2 mutations, with the exception of nine isolates. The msh2 mutations were identified in 68.8% (11/16) of the FR isolates and 67.4% (130/193) of the fluconazole susceptible-dose dependent isolates. There was no significant difference in all clinical characteristics between ST3 and ST7. However, the 30-day mortality of C. glabrata candidemia due to the two major ST (ST3 or ST7) strains was significantly higher than that of candidemia due to other minor ST strains (45.1 vs. 25.0%, p < 0.05). Multivariate logistic regression analysis also showed that two major STs (ST3 and ST7) were independent predictors of 30-day mortality. This study showed for the first time that two STs (ST7 and ST3) were predominant among BSI isolates in Korea, and that C. glabrata BSI isolates belonging to two major MLST genotypes are characterized by higher mortality. In addition, most msh2 mutations align with MLST genotype, irrespective of FR.

The Allplex Respiratory Panel 1/2/3 (All16) is a multiplex PCR assay for detecting 16 respiratory viruses with influenza A virus (FluA) subtyping, and the first clinical assay based on multiple detection temperatures. We compared the results between All16 and Anyplex II RV16 (Any16) in 426 clinical samples. Samples showing discrepancies between the two tests were further tested using monoplex PCR. FluA subtyping based on the hemagglutinin type results of All16, which yielded H1, H3, and non-H1/H3, was compared with the results of the BioFire FilmArray respiratory panel. The positive and negative percent agreements and kappa value for each virus between All16 and Any16 ranged from 54.5-100.0%, 84.7-100.0%, and 0.57-1.00, respectively. FluA subtype results from All16 for 26 samples were consistent with those from FilmArray. Good agreement was observed between the two methods, except when analyzing human enterovirus (kappa value 0.70), and the All16 showed reliable FluA subtyping results. For parainfluenza virus 3, the All16 was more sensitive than Any16. When testing 28 samples simultaneously, the mean test time and hands-on time were 4.3 and 0.5 hours, respectively in All16. In conclusion, All16 showed reliable performance, but further studies are needed regarding human enterovirus analysis.

Background We investigated the species distribution and amphotericin B (AMB) susceptibility of Korean clinical Aspergillus isolates by using two Etests and the CLSI broth microdilution method. Methods A total of 136 Aspergillus isolates obtained from 11 university hospitals were identified by sequencing the internal transcribed spacer (ITS) and β-tubulin genomic regions. Minimal inhibitory concentrations (MICs) of AMB were determined in Etests using Mueller-Hinton agar (Etest-MH) and RPMI agar (Etest-RPG), and categorical agreement with the CLSI method was assessed by using epidemiological cutoff values. Results ITS sequencing identified the following six Aspergillus species complexes: Aspergillus fumigatus (42.6% of the isolates), A. niger (23.5%), A. flavus (17.6%), A. terreus (11.0%), A. versicolor (4.4%), and A. ustus (0.7%). Cryptic species identifiable by β-tubulin sequencing accounted for 25.7% (35/136) of the isolates. Of all 136 isolates, 36 (26.5%) had AMB MICs of ≥2 µg/mL by the CLSI method. The categorical agreement of Etest-RPG with the CLSI method was 98% for the A. fumigatus, A. niger, and A. versicolor complexes, 87% for the A. terreus complex, and 37.5% for the A. flavus complex. That of Etest-MH was ≤75% for the A. niger, A. flavus, A. terreus, and A. versicolor complexes but was higher for the A. fumigatus complex (98.3%). Conclusions Aspergillus species other than A. fumigatus constitute about 60% of clinical Aspergillus isolates, and reduced AMB susceptibility is common among clinical isolates of Aspergillus in Korea. Molecular identification and AMB susceptibility testing by Etest-RPG may be useful for characterizing Aspergillus isolates of clinical relevance.

We developed a new scaffold for radionuclide-based imaging and therapy of clear cell renal cell carcinoma (ccRCC) targeting carbonic anhydrase IX (CAIX). Compound XYIMSR-01, a DOTA-conjugated, bivalent, low-molecular-weight ligand, has two moieties that target two separate sites on CAIX, imparting high affinity. We synthesized [111In]XYIMSR-01 in 73.8–75.8% (n = 3) yield with specific radioactivities ranging from 118 – 1,021 GBq/μmol (3,200–27,600 Ci/mmol). Single photon emission computed tomography of [111In]XYIMSR-01 in immunocompromised mice bearing CAIX-expressing SK-RC-52 tumors revealed radiotracer uptake in tumor as early as 1 h post-injection. Biodistribution studies demonstrated 26% injected dose per gram of radioactivity within tumor at 1 h. Tumor-to-blood, muscle and kidney ratios were 178.1 ± 145.4, 68.4 ± 29.0 and 1.7 ± 1.2, respectively, at 24 h post-injection. Retention of radioactivity was exclusively observed in tumors by 48 h, the latest time point evaluated. The dual targeting strategy to engage CAIX enabled specific detection of ccRCC in this xenograft model, with pharmacokinetics surpassing those of previously described radionuclide-based probes against CAIX.

Variant Philadelphia chromosome translocations involving chromosomes other than 9 and 22 have been reported in 5-10% of patients with chronic myeloid leukemia (CML). As part of the three-way variant t(9;22;11) in patients with CML, 11q24 is a novel region that has not previously been investigated. A 22-year-old male exhibiting chronic phase CML developed a recurrence of the same phase subsequent to the interruption of imatinib treatment and showed the same chromosomal abnormality, t(9;22;11)(q34;q11.2;q24), that was detected at the initial diagnosis. The recurrent CML responded well to imatinib therapy. These findings suggest that the three-way variant, t(9;22;11), involving 11q24 may be associated with a good prognosis and response to imatinib. This is the first report of three-way variant involving 11q24 in a patient with CML.

Group B streptococcus (GBS) is one of the leading causes of invasive infections in infants. This study aimed to investigate the genotypic diversity of GBS causing invasive infections in infants and to observe the prevalence of the highly virulent clone in South Korea.Invasive strains of GBS were collected prospectively from infants admitted at 4 hospitals during 1995-2015. Serotype and multilocus sequence typing were determined. All isolates underwent polymerase chain reaction amplification to detect the presence of the hypervirulent GBS adhesin (hvgA) gene. Antibiotic susceptibility testing was done by E-test, and erythromycin resistance genes were detected using polymerase chain reaction amplification.Among 98 GBS isolates collected, 14 sequence types (STs) were found; ST1 (20.4%), ST17 (19.4%) and ST19 (18.4%) were the most prevalent. The dominant serotype capsule expressed by ST1 was serotype V, ST17 and ST19 were all serotype III and ST23 was serotype Ia. hvgA gene was detected in 19.4% (n = 19) of the isolates; all were ST17, serotype III. A significant temporal trend of serotype III isolates was observed; as ST17 increased (P = 0.001) in proportion, ST19 decreased (P = 0.009). Erythromycin resistance was found in 42.9% (42/98); dominant strains were ermB-positive ST1 serotype V (n = 18/20, 90%), ermB-positive ST17 serotype III (n = 10/19, 52.6%) and ermA-positive ST335 serotype III (n = 7/7, 100%).The predominant STs causing invasive infections in South Korea were ST1, ST19 and ST17. Among serotype III isolates, an increase in proportion of the hypervirulent ST17 strains was observed. Erythromycin resistance was significantly associated with ST1.

Photonic microdisks with a multilayered structure are designed from photocurable suspensions by step-by-step photolithography. In each step of photolithography, either a colloidal photonic crystal or a magnetic-particle-laden layer is stacked over the windows of a photomask. Sequential photolithography enables the creation of multilayered photonic microdisks that have brilliant structural colors that can be switched by an external magnetic field.

Self-assembly of monodisperse colloidal particles into regular lattices has provided relatively simple and economical methods to prepare photonic crystals. The photonic stop band of colloidal crystals appears as opalescent structural colors, which are potentially useful for display devices, colorimetric sensors, and optical filters. However, colloidal crystals have low durability, and an undesired scattering of light makes the structures white and translucent. Moreover, micropatterning of colloidal crystals usually requires complex molding procedures, thereby limiting their practical applications. To overcome such shortcomings, we develop a pragmatic and amenable method to prepare colloidal photonic crystals with high optical transparency and physical rigidity using photocurable colloidal suspensions. The colloidal particles dispersed in a photocurable medium crystallized during capillary force-induced infiltration into a slab, and subsequent photopolymerization of the medium permanently solidifies the st...

Background At present, the clinical breakpoints (CBPs) of both fluconazole and voriconazole are available only for 3 common Candida species in the Clinical and Laboratory Standards Institute (CLSI) and the European Committee on Antimicrobial Susceptibility Testing (EUCAST) methods. Epidemiological cutoff values (ECVs) were recently applied to both methods to detect the emergence of acquired resistance (i.e., non-wild-type isolates) among 5 common Candida species. Methods We performed a nationwide study to determine the fluconazole and voriconazole susceptibility of Candida bloodstream isolates (BSIs) using both the CLSI and EUCAST methods. A total of 423 BSIs of 5 Candida species were collected from 8 hospitals. The azole susceptibilities were assessed on the basis of the species-specific CBPs and ECVs. Results Of the 341 BSIs of 3 common Candida species (i.e., C. albicans, C. tropicalis, and C. parapsilosis), 0.3% and 0.9%, 0.0% and 1.5% of isolates were categorized as fluconazole and voriconazole resistant according to the CLSI and EUCAST CBPs, respectively. Of 423 total BSIs, 1.4% and 2.6% had fluconazole minimum inhibitory concentrations (MICs) exceeding the ECVs according to the CLSI and EUCAST, respectively; 1.0% and 2.1% had voriconazole MICs exceeding the ECVs according to the CLSI and EUCAST, respectively. Categorical agreement between the methods using ECVs was 98.3% for fluconazole and 98.3% for voriconazole. Conclusions The EUCAST and CLSI methods using ECVs provide highly concordant results. Moreover, non-wild-type isolates with possibly acquired azole resistance were rare among the BSIs of 5 common Candida species in Korea.

We report a multidrug-resistant strain of Leclercia adecarboxylata responsible for catheter-related bacteremia in a 47-year-old female with breast cancer. The isolated strain was resistant to several β-lactams, aminoglycosides, and folate pathway inhibitors and harbored bla TEM-1 and bla CTX-M group 1 and intl1 genes ( dfrA12-orfF-aadA2 ) as genetic determinants for resistance. Based on a review of the L. adecarboxylata literature, there have been only 4 reports of antibiotic-resistant strains. To our knowledge, this is the first report of an L. adecarboxylata strain with simultaneous resistance to β-lactams, aminoglycosides, and sulfonamides.

Background : Malignant hyperthermia (MH) is genetically heterogeneous, with mutations in the gene encoding the skeletal muscle ryanodine receptor (RYR1) at 19q13.1 accounting for up to 80% of the cases. However, the search for known and novel mutations in the RYR1 gene is hampered by the fact that the gene contains 106 exons. We aimed to analyze mutations from the entire RYR1 coding region in Korean MH families. Methods : We investigated seven affected MH individuals and their family members. The entire RYR1 coding region from the genomic DNA was sequenced, and RYR1 haplotyping and mutational analysis were carried out. Results : We identified nine different RYR1 mutations or variations from seven Korean MH families. Among these, five previously reported mutations (p.Gly248Arg, p.Arg2435His, p.Arg2458His, p.Arg2676Trp, and p.Leu4838Val) and four novel variations of unknown significance (p.Arg2508Cys, p.Met4022Val, p.Glu2669Lys, and p.Ala4295Val) were identified. In two families, two variations (R2676W & M4022V, R2435H & A4295V, respectively) were identified simultaneously. Four of the observed nine mutations or variations were located outside the hotspot region of RYR1 mutations. Conclusions : These data indicate that RYR1 is a main candidate gene in Korean MH families, and that comprehensive screening of the entire coding sequence of the RYR1 gene is necessary for molecular genetic investigations in MH-susceptible individuals, owing to the presence of RYR1 mutations or variations outside of the hotspot region. (Korean J Lab Med 2010;30:702-10)

There have been very few multicenter studies of the relationship between the use of antifungals and resistance to them. We investigated the antifungal susceptibility of 1,301 clinical isolates of Candida collected from nine Korean hospitals during a 3-month period in 2006 to explore the existence of this type of relationship. Antifungal usage in the preceding year, defined as the daily dose per 1,000 patient days (DDD/1,000 PD), was calculated for each hospital. Resistance to fluconazole, itraconazole, and amphotericin B was detected in 2, 9, and 0.2% of the isolates, respectively. The MIC(50)/MIC(90) values were 0.03/0.125 mg/L for voriconazole, 0.06/0.25 mg/l for caspofungin, and 0.03/0.125 mg/l for micafungin. The total usage of systemic antifungals varied considerably among the nine hospitals, ranging from 6.1 to 96.2 DDD/1,000 PD. No relationship was found between the use of fluconazole (MICor =64 mg/l) or itraconazole (MICor =1 mg/l) and resistance in the Candida species (P0.05). However, significant correlations were found between the percentage of Candida isolates that were non-susceptible to fluconazole (MICor =16 mg/l) and fluconazole usage (r=0.733, P=0.025) or total antifungal usage (r=0.767, P=0.016).

Background : Immature platelet fraction (IPF) is the percentage of reticulated platelet (RP) of total platelet count. We measured an IPF reference range using XE-2100 blood cell counter with upgraded software (Sysmex, Japan) and evaluated the clinical utility of this parameter for the laboratory diagnosis of thrombocytopenia due to an increase in peripheral platelet destruction. Methods : Peripheral blood samples collected into K 2EDTA (Beckton Dickinson, USA) were analyzed at Chonbuk National University Hospital. One hundred forty-two samples from apparently healthy adults (all routine full blood count parameters including platelets within the healthy reference range) were used to establish a normal reference range for IPF. The patients were classified into 3 groups including hypoplastic (consisted of 22 patients undergoing chemotherapy with falling platelet counts and 14 with aplastic anemia), cirrhotic (40 with cirrhosis of liver), and idiopathic thrombocytopenic purpura (ITP) (14 with ITP) groups. Results : An IPF reference range in healthy individuals was established as 0.4-5.4%, with a mean of 1.7%. A significant increase in IPF values was found in the ITP patient group. The cut-off value of IPF was 6.1% and its sensitivity and specificity were 92.9%, and 82.9% respectively. Reproducibility was good. Conclusions : A rapid, inexpensive automated method for measuring IPF is feasible and should become a standard parameter in evaluating thrombocytopenic patients. (Korean J Lab Med 2007;27:1-6)

Isodicentric chromosomes are the most commonly reported aberrations of the human Y chromosome. We characterized the isodicentric Y chromosome from an azoospermic male by fluorescence in situ hybridization (FISH) and PCR. The patient was a 33-year-old man who visited our hospital for evaluation of infertility. He expressed male external genitalia and showed normal testosterone levels. However, severe varicocele on both sides and hydrocele of the right side were found upon ultrasonography of the scrotum, and no sperm were found on semen analysis. The patient showed 46,X,idic(Y)(q11.22)[58]/45,X[12] karyotype. FISH demonstrated the presence of two centromeres and two SRY regions (74.0% of cells counted). PCR showed the breakpoint between SY161 and SY121 in Yq11.221-q11.222.

We assessed the accuracy of yeast bloodstream isolate identification performed over a 1-year period at 10 South Korean hospitals, using the matrix-assisted laser desorption ionization–time of flight (MALDI-TOF)-based Vitek MS system. The overall phenotypic misidentification rate was 3.4% (18/533), with considerable variation between hospitals (0.0% to 19.0%), compared to 1.1% (6/533) for the Vitek MS system.

This study examined the serotype distribution and antimicrobial resistance of pneumococcal isolates from invasive infections in children between 2006 and 2010, when the 7-valent pneumococcal conjugate vaccine (PCV7) was offered as an optional vaccine in Korea. Among 140 isolates collected from 8 centers, the common serotypes were 19A (22.9%), 19 F (12.1%), and 6B (8.6%). Between 2006 and 2010, PCV7 serotypes decreased from 62.5% to 21.4% ( P = 0.002), whereas three 13-valent pneumococcal conjugate vaccine (PCV13)–specific serotypes (3, 6A, and 19A) increased from 18.8% to 42.9% ( P = 0.016). Among 102 multidrug-resistant isolates, the proportion of PCV7 serotypes decreased from 65.2% to 21.7% ( P = 0.001), and 3 PCV13-specific serotypes increased from 17.4% to 47.8% ( P = 0.008). Optional PCV7 vaccination has influenced the proportion of PCV7 serotypes in Korea, resulting in a decrease, whereas the proportions of 3 PCV13-specific serotypes, particularly 19A, have increased.

Objectives This study was performed to establish the reference intervals for whole blood viscosity (WBV) using the analytical performance-evaluated scanning capillary tube viscometer (SCTV). Design and methods The analytical performance of the SCTV was evaluated using three different levels of QC materials and sixty human EDTA-blood samples. To establish the reference intervals for WBV, 297 healthy individuals (123 men and 174 women) were selected from 1083 subjects. Results Within-day precisions with QC materials and human whole blood and between-day precisions with QC materials were below 5.0%, 6.6% and 8.0% in CVs at all shear rates, respectively. Comparison tests between the SCTV and the Brookfield viscometer showed a significant correlation (R 2 = 0.972, p − 1 and 23.15–36.45 cP at 1 s − 1 while those in women were 3.27–4.32 cP at 300 s − 1 and 18.20–27.36 cP at 1 s − 1 , respectively. Conclusions Using the analytical performance-evaluated SCTV, the reference intervals for WBV were established in healthy adults, which could be beneficial to the clinical utility of WBV in the aspect of appropriate modalities for the improvement of blood viscosity.

Carbonic anhydrase IX (CAIX) is a cell surface enzyme that is over-expressed in approximately 95% of clear cell renal cell carcinomas (ccRCCs), the most common renal cancer. CAIX is also a surrogate marker of hypoxic tumors for various human cancers; however, a clinically viable molecular imaging agent targeting CAIX is not available. We have synthesized and performed in vitro and in vivo evaluation of a dual-motif, low-molecular-weight inhibitor of CAIX, [64Cu] XYIMSR-06, for imaging CAIX expression on ccRCC tumors using positron emission tomography (PET). [64Cu] XYIMSR-06 was synthesized in two steps from reported dual-motif precursor 1. Upon radiolabeling, [64Cu] XYIMSR-06 was evaluated in immunocompromised mice bearing CAIX-expressing SK-RC-52 tumors for in vivo PET imaging and biodistribution. [64Cu] XYIMSR-06 was generated in radiochemical yields of 51.0 ± 4.5% (n = 5) and specific radioactivity of 6.0 GBq/μmol (170Ci/mmol ± 70, n = 5). Tumor could be visualized on PET images by 1 h post-injection with high tumor-to-background levels achieved within 24 h. Biodistribution studies of [64Cu] XYIMSR-06 demonstrated a maximum tumor uptake of 19.3 ± 4.51% injected dose per gram of radioactivity at 4 h. Tumor-to- blood, muscle and kidney ratios were 129.6 ± 18.8, 84.3 ± 21.0 and 2.1 ± 0.26, respectively, at 8 h post-injection. At 24 h, a tumor-to-kidney ratio of 7.1±2.5 was achieved. These findings represent increased tumor-to-background ratios at the indicated times relative to previously reported CAIX-targeted imaging agents. [64Cu] XYIMSR-06 is a promising candidate for PET imaging of CAIX expressing tumors, especially ccRCC. Citation Format: IL MINN, Soo Min Koo, Hye Soo Lee, Mary Brummet, Steven P. Rowe, Michael A. Gorin, Polina Sysa-Shah, William D. Lewis, Hye-Hyun Ahn, Yuchuan Wang, Sangeeta Ray, Ronnie C. Mease, Sridhar Nimmagadda, Mohamad E. Allaf, Martin G. Pomper, Xing Yang. A dual-motif CAIX inhibitor, [64Cu]XYIMSR-06, for PET imaging of clear cell renal cell carcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4206.

A 77-yr-old woman presented to the hospital with cough and dyspnea. Two years ago, she was diagnosed with non-small cell lung cancer and had been treated with wedge resection and several rounds of combined chemotherapy and radiation therapy. In the present visit, her initial diagnosis was bronchopneumonia with pleural effusion. Empirical antibiotic therapy by intravenous piperacillin/sulbactam was started. She was stable and afebrile during the intravenous antibiotic treatment. Findings of computed tomography of the chest and abdomen suggested multiple metastases in the liver, lymph nodes in the lesser omentum, and left supraclavicular lymph nodes. On day 22 of hospitalization, she developed fever of up to 38.1oC without any evident source and her vital signs and laboraINTRODUCTION

Orientia tsutsugamushi (O. tsutsugamushi), which is endemic to an Asia-Pacific region, has increased its incidence and caused annually around 10 thousand patients infected with scrub typhus in Korea in the past several years. In the present study, we isolated 44 O. tsutsugamushi from the patients with febrile illness accompanied with or without an eschar in Gyeongsangnam-do, Korea. These isolates were characterized by genetic analysis of the major outer membrane protein, the 56-kDa type-specific antigen (tsa56), which is unique to O. tsutsugamushi. Two types of sequences of tsa56, designated by JJ1 and JJ2, were determined from 37 and 7 isolates of the 44 isolates, respectively. JJ1 and JJ2 showed 74.7~90.8% identity in nucleotide sequence and 66.1~90.5% identity in amino acid sequence with 33 reference strains except for Boryong and Kuroki. JJ1 and JJ2 had 100 and 99.9% nucleotide identity to Boryong strain, and 99.9 and 99.8 % to Kuroki, which has been known to be similar to Boryong, respectively. In addition, they showed 77.9~ 81.4% nucleotide identity with the cluster of Gilliam-related genotypes, whereas they showed higher nucleotide identity (89.6~90.8%) with the cluster of Karp-related genotypes. To our knowledge, this is the first report to isolate O. tsutsugamushi and characterize their genotype as the Boryong in Jinju and West Gyeongsangnam-do, Korea, even though it has been reported that the Boryong was the predominant genotype in isolates from chiggers, domestic rodents, and patients in the southern part of Korea. Furthermore, our isolates could be useful source to study on the pathophysiology and epidemiology of scrub typhus in Korea.

Multilocus sequence typing (MLST) has been successfully applied to the epidemiology of Candida albicans isolates not only within the hospital setting but also in multiple locations nationwide. We performed MLST to investigate the genetic relatedness among bloodstream infection (BSI) isolates of C. albicans recovered from 10 Korean hospitals over a 12-month period. The 156 isolates yielded 112 unique diploid sequence types (DSTs). While 95 DSTs were each derived from a single isolate, 17 DSTs were shared by 61 isolates (39.1%). Interestingly, 111 (71.1%) isolates clustered within previously known clades, and 29 (18.6%) clustered within a new clade that includes strains of Asian origin previously typed as singletons. This MLST study was complemented by restriction endonuclease analysis of genomic DNA using BssHII (REAG-B) in order to evaluate whether strains with identical DSTs and originating from the same hospital corresponded to nosocomial clusters. Importantly, only those isolates with a strong epidemiological relationship showed ≥95% identical REAG-B types. Our results indicate that REAG-B typing can be complementary to MLST but should be limited to the investigation of isolates of identical DSTs and when interhuman transmission is suspected.

Background context Posterior lumbar interbody fusion (PLIF) using harvested local bone inserted into a polyetheretherketone (PEEK) cage is a commonly used procedure, but the accurate fusion rate of a cage, cage to bone contact area ratio, and the changes in fusion rate with time after surgery are unknown. Purpose The aim was to conduct a quantitative analysis of the fusion rates and the cage to bone contact area ratios at each period of time using a PEEK cage in PLIF using a consecutive three-dimensional (3D) computed tomography (CT) scan. Study design This was a prospective study using a consecutive 3D thin-section CT scan. Patient sample Thirty patients aged between 37 and 73 years set to undergo elective PLIF with PEEK cages and pedicle screw fixation were included in the study. Outcome measures The assessments included the Korean Oswestry Disability Index (K-ODI), Short Form (SF)-36 questionnaire, Visual Analog Scale (VAS) pain score, and dynamic plane radiographs, preoperatively and at 6 and 12 months after surgery. Methods Three-dimensional CT scans were performed at 6 and 12 months after surgery. Three-dimensional CT assessments of the following were performed: fusion rate of the cage, cage to bone contact area ratio, and fusion rate of the interbody bone graft besides the cage. Results The 6-month fusion rate of the segment was 86.7%, which increased to 90.0% at 12 months. The fusion area ratio between the cage area and end plate showed a significant increase from 52.0% at 6 months to 58.5% at 12 months. Regarding the fusion area ratio between the cage and end plate, the ratio between the lower surface of the cage was significantly higher than that of the upper surface. In addition, the K-ODI, SF-36, and VAS values were similar at 6 and 12 months after surgery. Conclusions The fusion rate of the PEEK cage used in PLIF measured at 12 months was higher than that measured at 6 months. Therefore, an assessment on the complete fusion of local bone at 12 months after surgery is more accurate.

The Beijing family of Mycobacterium tuberculosis has been emerging in the world. However, there are few nationwide data of genotypic distribution in Korea. This study aimed to identify the genotypic diversity of clinical isolates of M. tuberculosis and to demonstrate the population of Beijing family in Korea. We collected 96 clinical M. tuberculosis isolates from 11 university hospitals nationwide in Korea from 2008 to 2009. We observed 24 clusters in IS6110-RFLP analysis and 19 patterns in spoligotyping. Seventy-five isolates were confirmed to be Beijing family. Two isolates of the K strain and 12 isolates of the K family strain were also found. We found that drug resistance phenotypes were more strongly associated with Beijing family than non-Beijing family (P=0.003). This study gives an overview of the distribution of genotypes of M. tuberculosis in Korea. These findings indicate that we have to pay more attention to control of M. tuberculosis strains associated with the Beijing family.

Background In smokers, smoking causes many disease entities including cancers, chronic pulmonary diseases and cardiovascular diseases. Passive smoking is also accepted as a carcinogen and its adverse health effects are emphasized. We measured blood vitamin A, C, E (alpha-, beta- and gamma-tocopherol), coenzyme Q10 and urine cotinine concentrations in nonsmokers and smokers. Methods Twenty-one healthy nonsmokers and 24 healthy smokers were included in this study. Smoking status was assessed with a self-reported questionnaire. Plasma was analyzed for coenzyme Q10 and serum for vitamin A, C, E using HPLC (Agilent Technologies Inc., USA) and random urine for cotinine using LC/tandem mass spectrometry (Applied Biosystems Inc., Canada). Results Smokers had significantly lower serum concentrations of vitamin C than nonsmokers (P=0.0005). No significant differences in concentrations of serum vitamin A, E, and plasma coenzyme Q10 were observed. Smokers had highly elevated urine cotinine levels (1,454+/-903 ng/mL). In 16 (76.2%) of 21 nonsmokers, urine cotinine was detected (3.25+/-4.08 ng/mL). The correlations between urine cotinine and blood antioxidants levels were not found. Neither, the correlation between smoking status and blood antioxidants & urine cotinine was found. Conclusions This study shows that smokers had significantly lower vitamin C levels among nonenzymatic antioxidants, namely, vitamin A, C, E and coenzyme Q10. High detection rate of urine cotinine in nonsmokers show the seriousness of passive smoking exposure, therefore more social efforts should be directed to reduce passive smoking exposure.